As a thioglycerol compound possessing leukocyte increasing activity, Japanese Patent Unexamined Publication No. 46194/1992 describes the substance WS-1279A, represented by the formula: ##STR2##
Synthesis of WS-1279A was reported by Tsuda et al. [Chemical Pharmaceutical Bulletin, Vol. 39, pp. 607-611 (1991)] and Achiwa et al. [Japanese Patent Unexamined Publication No. 99796/1992; Chemical Pharmaceutical Bulletin, Vol. 39, pp. 2590-2596 (1991); Peptide Chemistry, pp. 361-366 (1991)]. In addition, Japanese Patent Unexamined Publication Nos. 9224/1979, 139348/1984, 6410/1990 and 9397/1992, Japanese Patent Examined Publication No. 60760/1988 and other publications describe thioglycerol compounds, but none describes leukocyte increasing activity.
Chemotherapy or radiotherapy on cancer patients can cause severe leukocytopenia or thrombocytopenia. Leukocytopenia, which results in impaired resistance to infectious and other diseases, and thrombocytopenia, which results in hemostatic dysfunction, both pose a major therapeutic problem for which no satisfactory treatment is available. There is therefore a need for a drug that promotes recovery of leukocyte or platelet count. There is another need for a drug offering rapid recovery of leukocyte count in bone marrow transplantation therapy and the treatment of osteomyelodysplasia. This kind of drug can also be used in the fields of thrombocytopenia following bone marrow transplantation and autoimmune diseases associated with platelet reduction, such as aplastic anemia and idiopathic thrombocytopenic purpura.
With this situation in mind, the present inventors designed and synthesized various compounds and investigated their leukocyte and platelet reduction recovering activity. As a result, the inventors found that a thioglycerol derivative promotes bone marrow cell growth to increase the peripheral leukocyte count and hence enhance immunity in mice, and that mouse megakaryocyte growth and differentiation can be promoted by stimulating bone marrow cells. The inventors made further investigations based on these findings, and developed the present invention.